2021 American Thyroid Association Guidelines for Management of Patients with Anaplastic Thyroid Cancer.

Background: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Since the guidelines for the management of ATC by the American Thyroid Association were first published in 2012, significant clinical and scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, and researchers on published evidence relating to the diagnosis and management of ATC. Methods: The specific clinical questions and topics addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of the Task Force members (authors of the guideline). Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations. Results: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, targeted/systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues, including end of life. The guidelines include 31 recommendations and 16 good practice statements. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of ATC. While all care must be individualized, such recommendations provide, in our opinion, optimal care paradigms for patients with ATC.

Research ethics dilemmas in thyroid disease.

PURPOSE OF REVIEW: Since research ethics dilemmas frequently fall outside the purview of the Institutional Review Board (IRB), we present three unique recent research ethics cases in thyroidology that demonstrate research ethics dilemmas. RECENT FINDINGS: The cases presented raise questions surrounding epistemic/scientific integrity, publication ethics, and professional, and personal integrity. SUMMARY: Research ethics dilemmas that fall outside the purview of the IRB are appropriate for a Research Ethics Consultation, a common service in many large academic medical centers.

Initiatives for Responding to Medical Trainees' Moral Distress about End-of-Life Cases.

Moral distress frequently arises for medical trainees exposed to end-of-life cases. We review the small literature on best practices for reducing moral distress in such cases and propose two areas to target for moral distress reduction: medical education and organizational ethics programs. Students require training in end-of-life dialogues and truthful prognostication, which are not generally available without skilled mentors. But physician-mentors and teachers can suffer from lingering moral residue themselves, which can affect the teaching culture and student expectations. Finally, reducing unit moral distress that affects learners requires formal educational opportunities to debrief about difficult end-of-life cases and formal institutional mechanisms for effective clinical ethics consultation.

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

INTRODUCTION: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. METHODS: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. RESULTS: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. CONCLUSIONS: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.

BACKGROUND: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. METHODS: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. RESULTS: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non-levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. CONCLUSIONS: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine-liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.

Ethical issues in the management of thyroid disease.

The focus of this article is on clinical ethics issues in the thyroid disease context. Clinical ethics is a subspecialty of bioethics that deals with bedside ethical dilemmas that specifically involve the provider-patient relationship. Such issues include consent and capacity; weighing therapeutic benefits against risks and side-effects; innovative therapies; end of life care; unintended versus intentional harms to patients or patient populations; and healthcare access. This article will review core ethical principles for practice, as well as the moral and legal requirements of informed consent. It will then discuss the range of unique and universal ethical issues and considerations that present in the management of autoimmune thyroid disease and thyroid cancer.

The end-of-life experiences of 9/11 civilians: death and dying in the World Trade Center.

This bioethics analysis of trapped civilians in the World Trade Center (WTC) on September 11, 2001, is based on a review of materials in the public domain. Death and dying experiences are divided into three major groups: sudden death, of which there was virtually no suffering or foreknowledge; deaths in which there was a maximum of 102 minutes of suffering; and death by falling or jumping, in which an autonomous decision may have been exercised as a palliative approach. A content analysis of publicly available records of this event reveals many types of end-of-life decisions were being made within the 102-minute time frame from aircraft impact to collapse. Many WTC occupants experienced intensified suffering directly consequent to unprepared emergency dispatchers and inaccurate instructions. Truthtelling and appropriate end-of-life dialogues could have reduced loss of life, suffering, and led to qualitatively improved dying experiences.

American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer.

BACKGROUND: Anaplastic thyroid cancer (ATC) is a rare but highly lethal form of thyroid cancer. Rapid evaluation and establishment of treatment goals are imperative for optimum patient management and require a multidisciplinary team approach. Here we present guidelines for the management of ATC. The development of these guidelines was supported by the American Thyroid Association (ATA), which requested the authors, members the ATA Taskforce for ATC, to independently develop guidelines for ATC. METHODS: Relevant literature was reviewed, including serial PubMed searches supplemented with additional articles. The quality and strength of recommendations were adapted from the Clinical Guidelines Committee of the American College of Physicians, which in turn was developed by the Grading of Recommendations Assessment, Development and Evaluation workshop. RESULTS: The guidelines include the diagnosis, initial evaluation, establishment of treatment goals, approaches to locoregional disease (surgery, radiotherapy, systemic therapy, supportive care during active therapy), approaches to advanced/metastatic disease, palliative care options, surveillance and long-term monitoring, and ethical issues including end of life. The guidelines include 65 recommendations. CONCLUSIONS: These are the first comprehensive guidelines for ATC and provide recommendations for management of this extremely aggressive malignancy. Patients with stage IVA/IVB resectable disease have the best prognosis, particularly if a multimodal approach (surgery, radiation, systemic therapy) is used, and some stage IVB unresectable patients may respond to aggressive therapy. Patients with stage IVC disease should be considered for a clinical trial or hospice/palliative care, depending upon their preference.

Pediatric ethics guidelines for hereditary medullary thyroid cancer.

Hereditary medullary thyroid cancer is an aggressive cancer for which there is no standard effective systemic therapy, but which can be prevented through genetic screening and prophylactic thyroidectomy. Although this cancer accounts for roughly 17% of all pediatric thyroid cancers, a significant percentage of affected families do not "accept" screening, while many gene carriers delay or refuse prophylactic thyroid surgery for their children. Current genetic screening practices in medullary thyroid cancer are inadequate; more than 50% of index patients with hereditary medullary thyroid cancer present with a thyroid mass; up to 75% have distant metastasis. These proposed pediatric ethics guidelines focus on two ethical issues that affect at-risk children: (1) how do we identify at-risk children whose RET-positive relative refuses to disclose that they carry the mutation? (2) How do we protect RET-positive children whose parents refuse prophylactic thyroidectomy?

Informed consent in the nuclear medicine setting.

In the nuclear medicine setting, the task of obtaining informed consent for procedures that require it is frequently left to the nuclear medicine technologist. Unfortunately, a patient's signature on a consent form does not mean the patient has given informed consent, or what legal scholars call valid consent. On completion of this scholarly bioethics article, the reader will understand the troubled history that led to informed consent as social and regulatory policy. Additionally, the reader will discover the meaning of "informed consent," which includes 3 critical components: disclosure, decision-making capacity, and voluntariness. Finally, this article will discuss which nuclear medicine procedures require informed consent, how to assess whether patients have given informed consent, what to do when the patient refuses a procedure, and what to do when informed consent is unachievable.

Ethical issues in radioisotope shortages: rationing and priority setting.

In recent years, shortages of radioisotopes that cannot be stockpiled have created a scenario in which they may be considered, periodically, a scarce medical resource. This discussion focuses on the just allocation of medical radioisotopes and presents the dominant ethical frameworks for rationing and priority setting in the patient populations most affected. Priority setting is necessary when demand for a scarce resource exceeds supply. On completion of this article, the reader will be able to describe the origins of rationing and priority setting in medicine, as well as ethically sound frameworks for rationing. Finally, the process for priority setting and the need for transparency of this process in the nuclear medicine setting are outlined.

The Suleman octuplet case: an analysis of multiple ethical issues.

The Suleman octuplet case is the first reported case in which surviving octuplets were born as a result of in vitro fertilization and embryo transfer. In this case, the octuplets were born to an American single mother of six children, who was on public assistance, and who used a sperm donor. This has raised multiple ethical questions, which include the ethical obligations of the health care providers involved, the informed consent process, as well as moral obligations of the mother to her existing children and unborn children. This case analysis provides a clinical ethics and prenatal ethics framework, based on relevant American media and public documents available from January 26, 2009, to January 26, 2010, the period of time in which media scrutiny of this case was most relevant. Although this analysis introduces broader ethical implications, it is not intended as a philosophical discourse regarding the rights of patients to reproduce or the rights of society to place limits on who can and who cannot reproduce; neither is it intended as an in-depth policy review of reproductive technologies. Rather, this analysis focuses on clinical ethics breaches in this particular case, which led to an unintended outcome. The relevant clinical ethical principles, duties, and obligations are identified, with recommendations for a preventative ethics approach in the absence of clear policies that regulate embryo transfer.

A preventive ethics approach to IVF in the age of octuplets.

A preventive ethics approach recognizes that ethical obligations of the in vitro fertilization practitioner should prevail, regardless of whether embryo transfer is regulated.

The Wiley Protocol: an analysis of ethical issues.

OBJECTIVE: : This review explores the ethical issues surrounding an unregulated protocol that is advertised to women through consumer books, the popular press, and the Internet, known as the Wiley Protocol. DESIGN: : A content analysis of relevant documents was conducted, followed by telephone interviews with investigators and former participants to verify facts. RESULTS: : The Wiley Protocol is an example of unregulated research involving potentially unsafe doses of bioidentical hormones applied to an unselected population of women. This protocol fails to use research ethics guidelines such as informed consent, investigator expertise, sound methodology, standardized data collection, and data safety monitoring. CONCLUSIONS: : Clinical ethics breaches include lack of full disclosure of risks, coercive influences, as well as misinformation about the study goals and safety. Breaches of professional ethics include conflicts of interest with respect to financial incentives, patient accrual, and inadequate standards of awareness and proficiency among participating investigators. It appears evident that the failure to regulate nutriceuticals and products of compounding pharmacy has provided the opportunity for these ethical violations.

The impaired hypothyroid patient: ethical considerations and obligations.

OBJECTIVES: Analyze the ethical duties and dilemmas involved in treating the severely hypothyroid patient. DESIGN: A critical review of the literature was conducted with respect to clinical ethics issues pertaining to severe hypothyroidism; legal and ethical guidelines for consent and capacity in the context of severe hypothyroidism; health case law involving the duty to warn third parties; and comparable clinical conditions resulting in impaired driving and the performance of critical tasks. MAIN OUTCOME: Neuropsychological studies and accepted clinical experiences verify the variable degrees of intellectual and neurological impairment consequent to severe hypothyroidism. Thus, severely hypothyroid patients are considered impaired in the performance of specific tasks, such as driving. Consequent to that, they may be agents of harm as a result of their impairment if they are not warned against driving or performing other duties affecting public safety. Severely hypothyroid patients may lack the capacity to make an informed decision, even when warned against driving or other tasks, and some may ignore such warnings. CONCLUSIONS: The legal and ethical "duty to warn" may trump confidentiality and HIPAA in cases where the activity of impaired patients seriously affects public safety. Not only do health care providers have a clear duty to warn patients not to drive, but in some extreme cases, may have a duty to warn third parties when a patient's driving or occupational duties place the public in harm's way.

Patient misconceptions and ethical challenges in radioactive iodine scanning and therapy.

The use and nature of radioactive iodine (RAI) are complex topics for patients with thyroid conditions to understand. Fear and anxiety over its use, misinformation in patient advocacy books and on the Internet, medical jargon, confusion regarding postscanning and posttreatment procedures, patient literacy, thyroid health status, and several other socioeconomic factors can create serious barriers to genuine informed consent in RAI scanning and treatment. The following discussion will review the origins of patient misconceptions and misinterpretations, including international differences in physician attitudes regarding RAI usage. Next, this article will present the core ethical duties, problems, and moral dilemmas that can arise in the RAI setting. Upon completion of this article, the reader should be able to describe the core ethical principles of respect for persons (patient autonomy), beneficence, nonmaleficence, and justice; describe the 3 components of informed consent; identify common barriers to informed consent and describe how such barriers can lead to misconceptions, misinformation, and refusal of treatment with RAI; and summarize where RAI candidates and patients first look for information and identify the common ways in which misinformation surfaces.

Inherited medullary thyroid cancer and the duty to warn: revisiting Pate v. Threlkel in light of HIPAA.

Familial medullary thyroid cancer (FMTC) is one of the few autosomal dominant cancers for which genetic testing provides a clear medical indication for prophylactic and/or curative therapy, and for which prophylactic thyroidectomy, followed by thyroid hormone replacement, presents a relatively low morbidity risk. Medullary thyroid cancer (MTC) is a particularly aggressive type of thyroid cancer, and screening by traditional biochemical markers yields a high proportion of advanced stage diagnoses in individuals from FMTC families. This is particularly hazardous since there are no curative systemic treatments for MTC. Genetic testing for germline mutations of the RET proto-oncogene provides a reliable method of identifying at-risk family members in those FMTC families in which a mutation has been identified in the proband. Prophylactic thyroidectomy in such at-risk family members has significantly reduced the proportion of advanced stage MTC diagnoses in MTC families. Since a clear medical benefit exists for genetic testing in family members, and a clear danger to family members exists in the absence of genetic counseling, establishing genetic diagnosis as standard of care has critical legal and ethical implications for medical providers caring for probands and family members. The "duty to warn," reinforced by the courts in the legal case of Pate v. Threlkel, may override recent confidentiality legislation, known as the HIPAA Privacy Rules, which came into effect April 12, 2003.